Bioreactor Engineering

1. Bioreactor configurations
2. Bioreactor operation modes
3. Practical considerations for
bioreactor design
Outline of Lecture
Bioreactor: device, usually a vessel, used to direct the activity of a
biological catalyst to achieve a desired chemical transformation.
Product
Bioreactor
Recycle
Product
separation & purification
Nutrients tank
Waste
Input
Pre-filtration
Fermenter: type of bioreactor
in which the biocatalyst is a
living cell.
What is a bioreactor?
1. Aerobic bioreactor: Need
adequate mixing and
aeration
2. Anaerobic bioreactor: no
need for sparging or
agitation
Challenges in Bioreactor Design
Bioreactor Configurations
- 1. Stirred tank
Mixing method: Mechanical
agitation
Baffles are usually used to
reduce vortexing
Applications: free and
immobilized enzyme
reactions
High shear forces may
damage cells
Require high energy input
Bioreactor Configurations
- 2. Bubble column
Mixing method: Gas
sparging
Simple design
Good heat and mass
transfer
Low energy input

Gas-liquid mass transfer
coefficients depend largely
on bubble diameter and gas
hold-up.
Bioreactor Configurations
- 3. Airlift reactor
Mixing method: airlift
Compared to bubble
column reactors, in an
airlift reactors, there
are two liquid steams:
up-flowing and down-
flowing steams. Liquid
circulates in an airlift
reactor as a resutl of
density difference
between riser and
downcomer.
Bioreactor Configurations
- 4. Packed-bed reactor
Packed-bed
reactors are used
with immobilized
or particulate
biocatalysts.

Medium can be
fed either at the
top or bottom and
forms a
continuous liquid
phase.
Bioreactor Configurations
- 5. Trickle-bed reactor
The trickle-bed
reactor is another
variation of the
packed bed
reactors.

Liquid is sprayed
onto the top of the
packing and
trickles down
through the bed in
small rivulets.
Bioreactor Configurations
- 6. Fluidized bed reactor
When the packed beds
are operated in upflow
mode, the bed expands
at high liquid flow rates
due to upward motion
of the particles.
Bioreactor Operation Modes
-1. Batch Operation
A batch bioreactor
is normally
equipped with an
agitator to mix the
reactant, and the
pH of the reactant
is maintained by
employing either
buffer solution or a
pH controller
S m
S s
C K
C r
dt
dC
r

max
t r C C
C
C
K
s s
s
s
m max 0
0
ln
Change of
Cs with time,
t
Batch
operation with
stirring
A foam breaker may be installed to disperse foam
Bioreactor Operation Modes
-2. Plug-flow mode
In a plug-flow
reactor, the
substrate enters
one end of a
cylindrical tube
with is packed with
immobilized
enzyme and the
product steam
leaves at the other
end.
t r C C
C
C
K
s s
s
s
m max 0
0
ln
F, Cs0
F, Cs
t = 0
F
V

An ideal plug-flow reactor can
approximate the long tube,
packed-bed and hollow fiber or
multistaged reactor
Residence
time
Continuous
operation without
stirring
V
Bioreactor Operation Modes
-3. Continuous stirred-tank
A continuous
stirred-tank reactor
(CSTR) is an ideal
reactor which is
based on the
assumption that
the reactants are
well mixed.
Continuous
operation with
stirring
F, Cs0
F, Cs
V
Bioreactor Operation Modes
-3. Continuous stirred-tank reactor-Con.
dt
dC
V V r FC FC
s
s s s

0
F, Cs0
F, Cs
V
Mass balance of substrate:
on Accumulati n Consumptio Output - Input
0
dt
dC
s
Steady state:
Michaelis-
Menten rate:
S m
S
C K
C r
r

max
0
max
0

s m
s
s s
C K
C r
V FC FC
Bioreactor Operation Modes
-3. Continuous stirred-tank reactor-Con.
s s
s
m s
C C
C r
K C

0
max

F, Cs0
F, Cs
V
Mass balance of substrate:
0
max
0

s m
s
s s
C K
C r
V FC FC

s m s s
s
C K C C
C r
V
F

0
max

V
F
kcal
Y
C V q
1

Heat production rate:
q
: heat production rate, kcal/ls
V: reactor liquid volume, l
: specific growth rate, s
-1
C: biomass concentration (g/l)
Y
kcal
: a yield coefficient given as
grams of cells formed per kcal energy
released, g cells/kcal
Heat load: Heat load is determined by energy balances
Practical Issues for Bioreactors
- Temperature Control (Heat Load)
Popular
method
Practical Issues for Bioreactors
-Temperature control (heat transfer)
Heat transfer surface area:
1. Low in (a) external jacket and (b) external coil for small reactors
2. High in (c) internal helical coil and (d) internal baffle coil for large reactors
3. Easily adjustable in (e) a separate external heat exchange unit
Difficult to clean
Easily fouled by cell
growth on the
surface
No cleaning problem

Sterility
requirement
Shear forces
imposed on cells
Depletion of
oxygen
1. Biological reactions almost invariably are three-phase reactions
(gas-liquid-solid). Effective mass transfer between phases is often
crucial. For example, for aerobic fermentation, the supply of
oxygen is critical.
H P C
g
A A

*

g
A A l A
C C K J
*
The equation governing the oxygen transfer rate is:
Agitation:
Mechanical stirring (for small reactors, and/or viscous liquids,
low reaction heat)
Air-driven agitation (for large reactors and/or high reaction heat)
Practical Issues for Bioreactors
-Agitation (gas transfer)
1. Mechanical foam
breaker (a
supplementary
impeller)
2. Chemical antifoam
agents (may
reduce the rate of
oxygen transfer)
Practical Issues for Bioreactors
- Foaming removal
1. Aseptic operation (3-5% of fermentations in
an industrial plant are lost due to failure of
sterilization.
2. Construction materials (glass for small
bioreactors, e.g., < 30 liters and corrosion-
resistant stainless steel for large reactors)
3. Sparage design (three designs: porous, orifice
and nozzle)
4. Evaporation control due to dry air input
Practical Issues for Bioreactors
- Other issues
Summary of Lecture
1. Bioreactor configurations
2. Bioreactor operation modes
3. Practical considerations for
bioreactor design